title: A novel exon 2 I27V VCP variant is associated with dissimilar clinical syndromes.
abstract: Mutations in valosin-containing protein (VCP) are associated with a syndromic constellation of inclusion body myositis, Paget's disease of bone and frontotemporal dementia. Here we describe the case reports of two patients with a novel variation (p.I27V) in the VCP gene that was not identified in a healthy control population. One patient presented with a frontotemporal dementia syndrome associated with raised serum alkaline phosphatase and a family history of progressive muscle disease and behavioural decline, while the second patient presented with isolated progressive dysarthria. Together these cases suggest a potential for the same VCP mutation to produce distinct patterns of brain damage, underlining the clinical heterogeneity of VCP-associated disease.
authors.affiliation: Dementia Research Centre, Institute of Neurology, Queen Square, London, WC1N 3BG, UK. rohrer@dementia.ion.ucl.ac.uk
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rohrer
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
authors.forename: David
authors.initials: D
authors.lastname: Reiman
authors.forename: James
authors.initials: J
authors.lastname: Uphill
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beck
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.forename: Martin N
authors.initials: MN
authors.lastname: Rossor
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Isaacs
authors.forename: Simon
authors.initials: S
authors.lastname: Mead
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D018797:Cell Cycle Proteins / Q000235:genetics*; D004401:Dysarthria / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein